Dendritic cell-derived IL-2 production is regulated by IL-15 in humans and in mice

• Published in: Blood 2005-01, Vol.105 (2), p.697-702
• Main Authors: Feau, Sonia, Facchinetti, Valeria, Granucci, Francesca, Citterio, Stefania, Jarrossay, David, Seresini, Samantha, Protti, Maria Pia, Lanzavecchia, Antonio, Ricciardi-Castagnoli, Paola
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; CD40 Antigens - metabolism; Cells, Cultured; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - metabolism; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Interleukin-15 - genetics; Interleukin-15 - metabolism; Interleukin-15 - pharmacology; Interleukin-2 - genetics; Interleukin-2 - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Modulation of the immune response (stimulation, suppression); Monocytes - cytology; RNA, Messenger - analysis; Signal Transduction - immunology; Specific Pathogen-Free Organisms
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2004-03-1059

Dendritic cells (DCs) are involved in the initiation and regulation of innate and adaptive immune responses. Several molecular mechanisms regulate these diverse DC functions, and we have previously reported that mouse dendritic cells (mDCs) can produce interleukin-2 (IL-2) in vitro and in vivo, in response to microbial activation and T-cell-mediated stimuli. This property is shared by different DC subtypes, including Langerhans cells. Here we show that, on appropriate stimulation, human DCs, both plasmacytoid and myeloid subtypes, also express IL-2. Interestingly, the production of IL-2 by myeloid DCs is induced by T-cell-mediated stimuli and depends on the presence of IL-15. The key role of this cytokine in regulating IL-2 production was also confirmed in the mouse system. In particular, we could show that DCs from IL-15-deficient mice were strongly impaired in the ability to produce IL-2 after interactions with different microbial stimuli. Our results indicate that DC-produced IL-2 is tightly coregulated with the expression of IL-15.